Term
|
Definition
|
|
Term
| cell-mediated immunity (cellular immunity) |
|
Definition
| responsible for defense against intracellular microbes, mediated by T cells |
|
|
Term
| T lymphocytes are found where in the lymph nodes? in spleen? |
|
Definition
paracortical areas
periarteriolar sheaths |
|
|
Term
| TCR, what does it recognize? |
|
Definition
(t cell receptor)
consist of an alpha and beta chain
recognizes MHC complex on surface of APCs |
|
|
Term
| can T cells be activated by soluble antigen? |
|
Definition
| no, must be presented with antigen in context of MHC..unless has ys chain |
|
|
Term
yS receptors
Found where? Require MHC? Recognize? |
|
Definition
only about 5 % of t cells express this type of TCR receptor that recognizes peptides, lipids, and small molecules
do NOT require display by MHC proteins
found on epithelial surfaces |
|
|
Term
|
Definition
secrete IL-2 and IFN-y
macrophage activation |
|
|
Term
|
Definition
secrete IL-4, IL-5, IL-13
activation of eosinophils and synthesis of IgE antibodies |
|
|
Term
|
Definition
secrete IL-17 and IL-22
powerful recruiters of neutrophils and monocytes |
|
|
Term
| where are B cells found in lymphoid tissue? in Spleen? |
|
Definition
peripheral lymphoid tissue
white pulp of spleen |
|
|
Term
| what do b cells turn into after activation? |
|
Definition
| plasma cells that secrete antibodies |
|
|
Term
| how are B cells activated? |
|
Definition
| T cells that express CD40 ligand bind to CD 40 on b cells and also produce cytokines to activate B cell maturation |
|
|
Term
|
Definition
| macrophages present peptide fragments of ags to T cells |
|
|
Term
|
Definition
macrophages are activated by IFN-y (produced by Th1 subset of CD4+ cells) and have enhanced microbicidal properties
OR
macrophages phagocytose microbes that are opsonized by IgG or C3b (humoral immunity) |
|
|
Term
| interdigitating dendritic cells |
|
Definition
express same chemokine receptors as T cells
express high levels of MHC class 2 to act as APCs
possess all necessary components for antigen presentation and activation of CD4+ cells |
|
|
Term
| follicular dendritic cells |
|
Definition
found in the GERMINAL CENTERS of lymphoid follicles
Express receptors for IgG and C3b
PRESENT ANTIGENS TO B CELLS and select B cells with the highest affinity for ag |
|
|
Term
|
Definition
large granular lymphocytes
capable of killing tumor cells, virally infected cells, and normal cells without prior sensitization |
|
|
Term
| antibody dependent cell-mediated cytotoxicity (ADCC) |
|
Definition
IgG coated cells are recognized by CD 16 of NK cells (Fc receptor for IgG) and kill cell
macrophages can also do this |
|
|
Term
| NK cells recognized MHC class _____ molecules of normal cells. |
|
Definition
| 1, thus inhibit activation |
|
|
Term
| Virally infected and tumor cells express stress-induced proteins such as |
|
Definition
| NKG2D, which stimulate NK cells and express MHC class 1 at reduced levels so there is no engagement of inhibitory receptors on NK cells |
|
|
Term
| Class 1 MHC molecules are expressed on ______ and bind to _____ T cells |
|
Definition
all nucleated cells and platelets
CD8+ |
|
|
Term
| What 3 loci encode class 1 mhc molecules? What chains compose them? What proteins do they display? Where is the peptide binding groove? |
|
Definition
HLA-A/B/C
alpha heavy chain and smaller B2 microglobulin
proteins from within cell (virally infected cells)
between alpha1 and alpha 2 |
|
|
Term
| Class 2 MHC molecules are expressed on ______ and bind to _____ T cells |
|
Definition
|
|
Term
| What 3 loci encode class 2 mhc molecules? What chains compose them? What proteins do they display? Where is the peptide binding groove? |
|
Definition
HLA-DP, HLA-DQ, HLA-DR
alpha and beta chain
exogenous antigens
alpha 1 and beta 1 |
|
|
Term
| HLA-B27 is associated with... |
|
Definition
|
|
Term
|
Definition
| Rheumatoid arthritis, Type 1 diabetes |
|
|
Term
| DR3 is associated with which disease |
|
Definition
| Sjogren syndrome, type 1 diabetes |
|
|
Term
| HLA-BW47 is associated with which metabolic deficiency |
|
Definition
| 21-hydroxylase deficiency |
|
|
Term
|
Definition
| immediate hypersensitivity |
|
|
Term
|
Definition
|
|
Term
| Type 3 hypersensitivity reaction |
|
Definition
| immune complex-mediated (antibodies bind antigens and activate complement) and elicit inflammation |
|
|
Term
|
Definition
| cell mediated (sensitized T cells cause cell and tissue injury) both CD4 (delayed type hypersensitivity) and CD8 (cell-mediated cytotoxicity) |
|
|
Term
| During type 1 hypersensitivity reactions, ag-ab complex binds to what cells? |
|
Definition
| mast cells (basophils of tissues) |
|
|
Term
| What are the 2 phases of Type 1 hypersensitivity reaction? |
|
Definition
Initial (immediate) that involves vasodilation, vascular leakage, smooth muscle spasm, glandular secretions that lasts 5-60 minutes
Late phase reaction-begins 2-24 hours later and can last for days, tissue infoltration by eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells causing tissue destruction |
|
|
Term
| Mast cells are found where? What do activates them? |
|
Definition
In subepithelial sites near blood vessels and nerves
activated by cross-linking of high-affinity IgE Fc receptors, C5a and C3a anaphylotoxins, physical stimuli, codeine and morphine |
|
|
Term
| What do T cells differentiate into after being exposed to antigen from dendritic cells in type 1 hypersensitivity reaction? What cytokine turns on IgE-producing B cells? activates eosinophils? promotes IgE production? |
|
Definition
|
|
Term
| Do IgE antibodies bind to mast cells? |
|
Definition
| yes, and their cross-linking when activated by antigen causes degranulation |
|
|
Term
| What are the primary mediators in mast cell granules? |
|
Definition
histamine (intesnse smooth muscle contraction, increased vascular permeability, increased secretion of glands)
enzymes such as neutral proteases, acid hydrolases
proteoglycans |
|
|
Term
| What are the secondary mediators in mast cell granules? |
|
Definition
Leukotrienes C4 and D4 (potent vasoactive spasmogenic, vasoconstriction and increased permeability)
Leukotriene B4 (chemotactic for neutrophils, monocytes, and eosinophils)
Prostaglandin D2 (bronchospasm and increased mucus secretion)
Platelet-activating factor (platelet aggregation, release of histamine, bronchospasm, increased vascular permeability, vasodilation, chemotactic for neutrophils and eosinophils) |
|
|
Term
| What are the 3 major products produced by eosinophils? |
|
Definition
| major basic protein, leukotriene C4, PAF |
|
|
Term
|
Definition
| predisposition to develop localized immediate hypersensitivity reactions to a variety of inhaled and ingested allergens |
|
|
Term
| atopy individuals have higher levels of.... |
|
Definition
IgE levels
IL-4 producing Th2 Cells
positive family history |
|
|
Term
| Type 2 hypersensitivity, opsonization and comoplement and Fc receptor-mediated phagocytosis (DEFINE and Examples) |
|
Definition
antibodies are deposited on cell surfaces, activate compliement (C3b and C4b) resulting in phgocytosis of opsonized cells
transfusion reactions
erythroblastosis fetalis
autoimmune hemolytic anemia
certain drug reactijons |
|
|
Term
| Type 2 hypersensitivity, complement and Fc Receptor mediated inflammation (DEFINE and Examples) |
|
Definition
antibodies deposit in extracellular tissues, activating compliment, C5a recruits inflammation
glomerulonephritis
vascular rejection in organ grafts |
|
|
Term
| Type 2 hypersensitivity, antibody-mediated cellular dysfunction(DEFINE and Examples) |
|
Definition
antibodies impair cell function without causing injury or inflammation
myasthenia gravis
pemphigus vulgaris (abs against desmosomes disrupt intercellular junctions in the epidermis causing vesicle formation)
graves disease |
|
|
Term
| examples of immune complex disorders (type 3 hypersensitivity) |
|
Definition
systemic lupus erythematosus
polyarteritis nodosa
poststreptococcal glomerulonephritis |
|
|
Term
| what are the favored sites for systemic immune complex deposition? |
|
Definition
where blood is filtered at high pressure to form other fluids
glomeruli and joints! |
|
|
Term
| local immune complex disease (arthus reaction) |
|
Definition
| type 3 hypersensitivity, localized area of tissue necrosis due to acute immune complex vasculitis (usually occurs in the skin) |
|
|
Term
| local immune complex disease (arthus reaction) is characterized by what type of inflammation |
|
Definition
| fibrinoid necrosis, acute necrotizing vasculitis that appears as smudgy, pink material under microscope |
|
|
Term
| what is the classical example of delayed-type hypersensitivity? |
|
Definition
| tuberculin reaction (TB infection) where CD4 positive cells (helper T cells) are activated and recruit macrophages for granuloma formation |
|
|
Term
| granuloma formation is characterisitic of what type of hypersensitivity reaction |
|
Definition
|
|
Term
| What kind of T cells are abundant in delayed type hypersensitivity? |
|
Definition
| Th1 (CD4+ helper T cells) |
|
|
Term
| What are the major cytokines produced by TH1 cells during delayed type hypersensitivity? |
|
Definition
|
|
Term
| cell-mediated cytotoxicity (CD8+ cells)is what type of hypersensitivity reaction? |
|
Definition
| T Cell-Mediated (Type 4) hypersensitivity |
|
|
Term
| what are the two ways cytotoxic T lymphocytes cause cell death? |
|
Definition
perforin-granzyme-dependent killing
fas-fas ligand killing |
|
|
Term
| describe the perforin-granzyme-dependent killing mechanism of CTLs |
|
Definition
| peforins drill holes in cell, releasing water and granzymes. Granzymes activate caspases that cause cell apoptosis. |
|
|
Term
| what are some examples of cell-mediated cytotoxicity? |
|
Definition
resistance to virus-infected cells
transplant rejection
tumor immunity |
|
|
Term
| what are the 3 requirements for autoimmune disease? |
|
Definition
1. presence of an autoimmune reaction
2. evidence that it is not secondary to tissue damage
3. absence of another well-defined cause of the disease |
|
|
Term
| systemic lupus erythematosus is a type of ____disease |
|
Definition
|
|
Term
| multiple sclerosis attacks... |
|
Definition
|
|
Term
| central vs. peripheral tolerance |
|
Definition
central deletes self-reactive t and b cell clones in thymus and bone during maturation
peripheral are self reactive t cells that escape negative selection and must be silenced before they damage tissues |
|
|
Term
|
Definition
| prolonged or irreversible functional inactivation of lymphocytes |
|
|
Term
|
Definition
| a population of CD4+ T cells that prevent immune reactions against self-antigens, express CD25 |
|
|
Term
| what are the 3 ways peripheral tolerance is accomplished? |
|
Definition
1. suppression by regulatory T cells
2. clonal detection by activation-induced cell death
3. antigen sequestration (eye, testes, brain) |
|
|
Term
| what is epitope spreading? |
|
Definition
| infections mess up self-antigens, exposing a previously hidden epitope, activating new lymphocytes that begin attacking all over |
|
|
Term
| why would an infection bring about auto immunity? |
|
Definition
1. up-regulation of costimulator expression (hyperactive state) may cause breakdown of clonal anergy
2. molecular mimicry |
|
|
Term
| Systemic lupus erythematosus primarily effects men or woman? what organs? |
|
Definition
women (african-american 20-30 y/o)
skin, joints, kidneys, serosal membranes |
|
|
Term
| what is the defect in systemic lupus erythrematosus? |
|
Definition
| failure of the mechanisms that maintain self-tolerance |
|
|
Term
| antinuclear autoantibodies |
|
Definition
all patients with SLE have these, they are antibodies directed against:
DNA, hostones, nonhistone proteins bound to RNA, nucleolar antigens |
|
|
Term
| rim or peripheral staining is indicative of... |
|
Definition
|
|
Term
|
Definition
| shows up as speckled staining, abs to non-DNA nuclear constiuents |
|
|
Term
| Antibodies to ____ and ____ have a very high correlation with SLE |
|
Definition
|
|
Term
| SLE patients often have antibodies not only to DNA or sm antigen, but also ______ which can cause ______ |
|
Definition
antiphopholipid antibodies
secondary antiphophlipid ab syndryome (hypercoagulability) |
|
|
Term
| what environmental factors enhance SLE response? |
|
Definition
drugs
UV radiation
Sex hormones (i.e during pregnancy) |
|
|
Term
|
Definition
| nuclei of damaged cells react with ANAs (antinuclear angibodies), lose their chromatin pattern, and appear homogenous |
|
|
Term
|
Definition
| any phagocytic cell that has engulfed the denatured nucleus of an injured cell, often found in pleural or pericardial effusions |
|
|
Term
| Renal injury in SLE classifications |
|
Definition
Class 1- minimal or no detectable abnormalities
Class 2-mesangial lupus glomerulonephritis (mild hematuria or transient proteinuria, MESANGIAL CELL PROLIFERATION without involvement of glomerular capillary walls, grandular mesangial deposits of immunoglobulin and complement are always present)
Class 3: Focal proliferative glomerulonephritis ( affects less than 50% of glomeruli and only portions of each affected glomerulus, SWELLING AND PROLIFERATION OF ENDOTHELIAL AND MESANGIAL CELLS) infiltratin by neutrophils
Class 4: most serious, proteinuria hematuria and hypertension, renal insufficiency, diffuse lesions, fibrinoid necrosis, proliferation of endothelial mesangial and epithelial cells, EPITHELIAL CRESCENTS, apoptotic bodies, hyaline thrombi
Class 5: severe proteinuria or nephrotic syndrome, widespread thickening of capillary walls |
|
|
Term
| what is a wire-loop lesion? |
|
Definition
| extensive, confluent subendothelial deposits create a uniform thickening of the capillary wall (in SLE glomerululs) |
|
|
Term
| where is the damage done in the skin for SLE patients? |
|
Definition
| dermal-epidermal junction (DE) and degeneration of the basal layer of the epidermis with edema at the DE junction |
|
|
Term
| What are some cardiovascular changes seen with SLE patients? |
|
Definition
pericarditis is the most common
acceleraated coronary atherosclerosis
libman-sacks endocarditis |
|
|
Term
| Libman-sacks endocarditis |
|
Definition
| nonbacterial valvular vegetations that look like 1-3mm warty deposits (in SLE patients) |
|
|
Term
| what is the clinical course of SLE? |
|
Definition
classic: female with butterfly rash, joint pain, fever, pleuritic chest pain, and photosensitivity
death by renal failure, multiple infections, coronary artery disease |
|
|
Term
| chronic discoid lupus erythematosus |
|
Definition
disease is confined to the skin, some will later develop multisystem disease
ds DNA abs rare, 35% show positive ANA test |
|
|
Term
| subacute cutaneous lupus erythematosus |
|
Definition
skin involvement is predominant
HLA-DR3 and abs to SS-A strong association |
|
|
Term
| drug-induced lupus erythematosus |
|
Definition
predisposed people when take:
hydralazine, procainamide, isoniazid, D-penicillamine
HLA-DR4 with hydralazine, antihistone abs
disease goes away after the drug is withdrawn |
|
|
Term
| sjogren syndrome effects which two glands |
|
Definition
|
|
Term
|
Definition
| decreased tears and saliva |
|
|
Term
| sjorgrens appears primarily in _____ woman |
|
Definition
|
|
Term
| 90% of sjogrens patients have antibodies to _____ |
|
Definition
| ribonucleoprotein antigens |
|
|
Term
| Sjogren patients with antibodies to SS-A have a _____ onset, _____ duration, and _____ manifestations. |
|
Definition
| earlier, longer, extraglandular |
|
|
Term
| sjorgrens is initiated by _____ cells |
|
Definition
|
|
Term
|
Definition
|
|
Term
| sjorgrens patients have a 40x increased risk of developing ____ |
|
Definition
|
|
Term
|
Definition
| combination of lacrimal and salivary gland enlargement due to any cause (sarcoidosis, leukemia, lymphoma, other tumors) |
|
|
Term
|
Definition
| scleroderma, abnormal accumulation of fibrous tissue in the skin and multiple organs |
|
|
Term
|
Definition
| widespread skin involvement with rapid progression and EARLY VISCERAL INVOLVEMENT |
|
|
Term
|
Definition
| skin involvement usually confined to the fingers, forearms, and face |
|
|
Term
| people with systemic sclerosis may develop.... |
|
Definition
CREST syndrome
calcinosis
raynaud phenomenon
esophageal dysmotility
sclerodactyly
telangiectasia |
|
|
Term
| what is the basis for systemic sclerosis? |
|
Definition
| CD4+ cells respond to an unidentified ag, release cytokins, recruiting inflammatory cells and fibroblasts, fibrosis and scarring occurs |
|
|
Term
|
Definition
| ab to DNA topoisomerase, often found in patients with diffuse scleroderma |
|
|
Term
|
Definition
| found in patients with CREST or limited scleroderma |
|
|
Term
| Describe the progression of scleroderma |
|
Definition
atrophy begins in the fingers, raynaud phenomenon seen in all patients and usually first symptom
edematous skin, progressing to fibrosis of dermis
epidermis thins
in advanced stages fingers become tapered and claw-like with limited range of motion and face becomes taut like a mask |
|
|
Term
Organs also affected by scleroderma (variable):
GI
Kidneys
Lungs
Heart |
|
Definition
GI: muscularis replaced by collagen, most severe is esophagus lower 2/3 becoming firm and inflexible, malabsorption syndrom because of loss of villi in small bowel
KIDNEYS: intimal thickening due to collagen, hypertension and renal failure
LUNGS: fibrosis, pulmonary hypertension
HEART: pericarditis, myocardial fibrosis |
|
|
Term
| What patients are at a higher risk to get scleroderma? |
|
Definition
| woman 3x, 50-60 years of age |
|
|
Term
| Major cause of death for scleroderma patients: |
|
Definition
| pulmonary disease, renal failure |
|
|
Term
| mixed connective tissue disease have high titers of______ and have little to no _____ |
|
Definition
anti-U1 RNP abs
renal disease (respond well to corticosteroids) |
|
|
Term
|
Definition
| autoimmune disease with necrotizing inflammation of blood vessel walls |
|
|
Term
| Transplant rejection is based on recognizing ____ system molecules as foreign. |
|
Definition
|
|
Term
| What type of hypersenstivity reaction is transplant rejection? What types of T-cells are involved? |
|
Definition
type 4 (delayed)
CD4+ (delayed hypersensitivity) and CD8+ (destruction of graft cells) |
|
|
Term
| Direct pathway (T Cell mediated) for Transplant reaction |
|
Definition
CD8+ cells recognize class 1 HLA and kill grafted tissues directly by maturing to CTLs
OR
CD4+ cells recognize class 2 HLA and differentiate into TH1 cells, activating macrophages
usually more prominent in acute rejection |
|
|
Term
| Indirect pathway (T Cell mediated) for Transplant reaction |
|
Definition
| Memory CD4+ T cells are presented with antigen, release cytokines, and is a delayed type hypersensitivity associated with chronic rejection |
|
|
Term
| Antibody-mediated destruction of transplant tissue |
|
Definition
hyperacute and acute, preformed abs are already in circulation due to previous transplant rejection, previous blood transfusions, multiparous woman
results in quick thrombosis and ischemic death of the graft |
|
|
Term
| what is the morphology of a hyperacute rejection |
|
Definition
| occurs within minutes-hours, immunoglobulin and complement are deposited in the vessel wall, thrombi form, fibrinoid necrosis in arterial walls |
|
|
Term
|
Definition
| initial target of abs is the fraft vasculature |
|
|
Term
| chronic rejection will show a progressive rise in serum _____ levels over 4-6 months |
|
Definition
|
|
Term
|
Definition
blocks activation of a transcription factor required for transcription of cytokines
inhibits leukocyte development in the bone marrow |
|
|
Term
| For the transplanted kidney, HLA matching is key. For other solid organs, ____ and ____ are more important than HLA matching. |
|
Definition
organ size
organ availability |
|
|
Term
| what are the 3 settings in which graft-vs-host disease can occur? |
|
Definition
1. bone marrow transplants
2. solid organs rich in lymphoid cells
3. transfusion of non-irradiated blood |
|
|
Term
| What causes the reaction seen in GVH disease? |
|
Definition
| immunocompetent donor T cells recognize the recipients HLA antigens as foreign and react against them |
|
|
Term
| Acute and Chronic GVH disease affect what primarily |
|
Definition
| epithelia of skin, liver, and intestines |
|
|
Term
| What is the consequence of profound immunosuppression that accompanies GVH? |
|
Definition
| recurrent and life-threatening infections, especially with CMV induced pneumonitis (fatal) |
|
|
Term
| What is the defect in X-linked agammaglobulinemia of Bruton? What is the consequence of this mutation? |
|
Definition
Bruton tyrosine kinase
B cell precursors fail to mature into B cells |
|
|
Term
| Which chains are produced in Agammaglobulinemia of Bruton? |
|
Definition
| only heavy chains, light chains are NOT produced |
|
|
Term
| What disease is characterized by absent mature B cells and plasma cells, as well as low serum levels of all classes of Igs? |
|
Definition
| X-linked agammaglobulinemia of Bruton |
|
|
Term
| What immunodeficiency is characterized by the inability to differentiate into plasma cells? |
|
Definition
| common variable immunodeficiency (hypogammaglobulinemia) |
|
|
Term
| Which immunodeficiency has an increased risk of gastric and lymphoid cancers and affects both males and females the same? |
|
Definition
| common variable immunodeficiency (hypogammaglobulinemia) |
|
|
Term
| Isolated IgA deficiency is a common disorder among ____. Patients have weakened_____ defense, although most people are completely ____ |
|
Definition
caucasians
weakened mucosal defense
asymptomatic |
|
|
Term
| Which immunodefieciency is characterized by a failure of isotype switching? |
|
Definition
|
|
Term
| Hyper IgM syndrome have a mutation (70%) of _____ located on the ____ chromosome |
|
Definition
|
|
Term
| DiGeorge syndroe is characterized by a loss of ______ immunity. This results in a weakened defense mechanism against _____and_____ infections. These patients also have a lack of which gland? |
|
Definition
T Cell mediated
fungal and viral
parathyroid |
|
|
Term
| A baby presents with rash, thrush, and failure to thrive. This is most consistent with which inherited immunodefieciency> |
|
Definition
| severe combined immunodeficiency disease (SCID) |
|
|
Term
| Defective IL-7 receptor signaling and reduced T cell population is characteristic of which immunodeficiency? |
|
Definition
| severe combined immunodefieciency diseases (SCID) |
|
|
Term
| Thrombocytopenia, eczema, low IgM, normal IgG, and high IgA and IgE with an increased risk of developing malignant lymphomas is characteristic of which inherited immunodeficiency? |
|
Definition
Wiskott-Aldrich Syndrome
x-linked recessive |
|
|
Term
| Increased susceptibility to neisserial infections is a result of a deficiency of _____ |
|
Definition
|
|
Term
| Deficiency of C1 inhibitor with production of vasoactive peptides is known as_____ |
|
Definition
|
|
Term
| Coreceptors on CD4+ cells for HIV |
|
Definition
|
|
Term
| What is primary amyloidosis? |
|
Definition
most common type
systemic distribution of AL type amyloid
comon in multiple myeloma, M protein spike can be seen on serum electrophoresis |
|
|
Term
| What is secondary amyloidosis? |
|
Definition
| reactive systemic amyloidosis of AA type amyloid, secondary to an inflammatory condition |
|
|
Term
| what is responsible for hemodialysis associated amyloidosis? |
|
Definition
deposition of B2 microglobulin
cannot be filtered through dialysis membranes |
|
|
Term
| amyloid of aging often has a significant _____ involvement |
|
Definition
|
|
Term
| what is the major cause of death in amyloidosis patients/ |
|
Definition
| renal involvement (amyloid deposition in glomeruli causing proteinuria and destruction of glomerular architecture and capillary lumens |
|
|
